Exploring the heterogeneity of the vaccine-elicited T cell response by scRNAseq

PROJECT SUMMARY Clinically relevant cellular responses to either experimental or FDA approved vaccine adjuvant formulations have been difficult to generate and/or detect. Given the robust cellular responses against infectious challenge, a reasonable assumption is that subunit vaccine formulations will better achieve cellular responses by following

the established rules governing the response to infections. However, we have shown that subunit vaccine- elicited T cell responses are dependent on numerous factors (cytokines, transcription factors, metabolic pathways) which are irrelevant, or even restrictive, to the T cell response to infectious challenge. More recent

preliminary scRNAseq results suggest that subunit vaccination generates an entirely unique population of T cells unobserved in response to infectious challenge, capable of rapid, robust, and enduring memory formation. The present proposal will examine the heterogeneity of both vaccine-elicited and infection-elicited T

cell responses over time, to what degree this heterogeneity overlaps with each other, and whether or not specific T cell populations are predictive of an adjuvants' capacity for eliciting T cells and therefore be useful in stratifying adjuvants along the axis of protective CD8+ T cell memory generation.